considering the best knowledge of the factors and their consequences and bodily
responses to the parameterized characteristics of nanomedicines and radionanomedicines. The contents in the chapters would be a description of the efforts to
understand the in vivo behavior of nanomaterials from the different perspectives.
People used to develop new nanomaterials first and feel happy with the implication
of these nanomaterials which might be used in humans for clinical purposes. And
they are frustrated with the general dis-knowledge of our field of the behavior of
nanomaterials in vivo. The accumulation of the reports in the literature should have
been understood in reasonable way and readers can encounter the description
meticulously prepared. Size and shape was critical for the clinical application of a
type of silica nanoparticles and the radiating tracks of novel endeavor to develop
other nanomedicines were supposed to take place based on this knowledge.
PEGylation or newer zwitterionic modification is now popular practice to make
nanomaterials biocompatible, more specifically hydrophilic, hiding from the trapping or immune responses of the body. The stealth effect of these modifications was
once coined to exaggerate the hope to deceive the bodily non-immune or immune
surveillance system. This idea is going through reality testing and the readers can
get the summary of the progress including the most recent achievements.
Nanomaterials were not inert in systemic circulation and recent proteomic analysis
even enabled fingerprinting of the constitution of wrapping plasma proteins around
nanomedicines. In our long tradition of developing new radiopharmaceuticals using
small molecules or biomacromolecules, it was customary to add the biodistribution
data made of histograms associated with representative, gamma camera, SPECT or
PET images of the small animals. For nanomedicines and radionanomedicines, the
same customs are repeatedly exercised by many investigators; however, in the
chapter ‘Excretion and Clearance’, readers can now learn the framework regarding
how to comprehend the behavior of novel nanomedicines and radionanomedicines
in vivo. Caveat was that we should not automatically assume that liver uptake is the
clearance by mononuclear phagocytic system. Hepatobiliary clearance was
repeatedly reported in the literature but without proper emphasis on their significance. Renal or other peripheral clearance by non-phagocytic cells should be kept
in mind to correctly interpret the excretion and clearance.
Immune response to the exogenous or endogenous nanomaterials must be
explained with the best knowledge of versatility of diverse immune surveillance
system of human as well as animals. Doxorubicin-containing liposomes had been
clinically used for more than 2 decades now and taught the scientific and medical
community very well, and thus we understand the details of the immune response to
the challenges by exogenous drug-containing liposomes systemically administered
to patients. Interestingly, first-line of response was non-specific reactions including
complement and other cascade protein system in the plasma. This was followed by
less-specific humoral immune response of IgM. We now know the first encounter
can elicit mild to serious even fatal reaction to the similar kind of liposomal constructs and second injection will meet humoral or other well-known adaptive
immunity of the body. In the meantime, most recently, the understanding of innate
immunity and adaptive immunity and their differentiation was totally changed.
8
D. S. Lee
responses to the parameterized characteristics of nanomedicines and radionanomedicines. The contents in the chapters would be a description of the efforts to
understand the in vivo behavior of nanomaterials from the different perspectives.
People used to develop new nanomaterials first and feel happy with the implication
of these nanomaterials which might be used in humans for clinical purposes. And
they are frustrated with the general dis-knowledge of our field of the behavior of
nanomaterials in vivo. The accumulation of the reports in the literature should have
been understood in reasonable way and readers can encounter the description
meticulously prepared. Size and shape was critical for the clinical application of a
type of silica nanoparticles and the radiating tracks of novel endeavor to develop
other nanomedicines were supposed to take place based on this knowledge.
PEGylation or newer zwitterionic modification is now popular practice to make
nanomaterials biocompatible, more specifically hydrophilic, hiding from the trapping or immune responses of the body. The stealth effect of these modifications was
once coined to exaggerate the hope to deceive the bodily non-immune or immune
surveillance system. This idea is going through reality testing and the readers can
get the summary of the progress including the most recent achievements.
Nanomaterials were not inert in systemic circulation and recent proteomic analysis
even enabled fingerprinting of the constitution of wrapping plasma proteins around
nanomedicines. In our long tradition of developing new radiopharmaceuticals using
small molecules or biomacromolecules, it was customary to add the biodistribution
data made of histograms associated with representative, gamma camera, SPECT or
PET images of the small animals. For nanomedicines and radionanomedicines, the
same customs are repeatedly exercised by many investigators; however, in the
chapter ‘Excretion and Clearance’, readers can now learn the framework regarding
how to comprehend the behavior of novel nanomedicines and radionanomedicines
in vivo. Caveat was that we should not automatically assume that liver uptake is the
clearance by mononuclear phagocytic system. Hepatobiliary clearance was
repeatedly reported in the literature but without proper emphasis on their significance. Renal or other peripheral clearance by non-phagocytic cells should be kept
in mind to correctly interpret the excretion and clearance.
Immune response to the exogenous or endogenous nanomaterials must be
explained with the best knowledge of versatility of diverse immune surveillance
system of human as well as animals. Doxorubicin-containing liposomes had been
clinically used for more than 2 decades now and taught the scientific and medical
community very well, and thus we understand the details of the immune response to
the challenges by exogenous drug-containing liposomes systemically administered
to patients. Interestingly, first-line of response was non-specific reactions including
complement and other cascade protein system in the plasma. This was followed by
less-specific humoral immune response of IgM. We now know the first encounter
can elicit mild to serious even fatal reaction to the similar kind of liposomal constructs and second injection will meet humoral or other well-known adaptive
immunity of the body. In the meantime, most recently, the understanding of innate
immunity and adaptive immunity and their differentiation was totally changed.
8
D. S. Lee